This proposal is concerned with studies of various aspects of hypothalamic-pituitary-thyroid physiology in health and disease. Specific areas of current and planned investigation include: 1) Studies of the effects of various pharmacological agents and metabolic inhibitors on thyroxine (T4) conversion to triiodothyronine (T3) in rat liver and kidney homogenates and isolated liver cells. 2) Purification of rat liver and kidney T4-5'-deiodinating enzyme(s). 3) Studies of the effects of various pharmacological agents, hormones and nutritional variables on pituitary-thyroid physiology in normal human subjects and patients with thyroid and other diseases. 4) Comparison of the early effects of T4 and T3 on hormonal and other parameters in patients with hypothyroidism. 5) Attempts to define the pathophysiology of changes in thyroid function and physiology in patients with nonthyroid illness. 6) Studies of the forms of thyrotropin-releasing hormone (TRH) immunoreactivity in hypothalamic tissue.